Chemical Dependencya New Paradigm

Richard L. Hinchman, M.D., FACOG, FASAM

Your Brain on Drugs in the 1980’s

What the mind does not know, the eyes cannot see

If drugs and alcohol were the problem

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Animal ModelsAnimal Models

Alcohol (P) Preferring MiceAlcohol (P) Preferring Mice Alcohol (NP) Non-preferring MiceAlcohol (NP) Non-preferring Mice

DA measurement in NADA measurement in NA

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Positron Emission Tomography (PET)Positron Emission Tomography (PET)

Human StudiesHuman Studies

PET scans of sons of alcoholic fathersPET scans of sons of alcoholic fathers Sons were naïve to alcoholSons were naïve to alcohol 40% had lower Dopamine (DA) levels 40% had lower Dopamine (DA) levels

when compared to controls when compared to controls

Quick ReviewQuick Review Dependence is a Primary DiseaseDependence is a Primary Disease 40% to 60% genetic predisposition40% to 60% genetic predisposition Not located in judgment area of brainNot located in judgment area of brain Located in the mid-brain (Located in the mid-brain (survivalsurvival)) Mid-brain controls the judgment areaMid-brain controls the judgment area DA Deficiency is underlying pathologyDA Deficiency is underlying pathology Treatment must maintain DA levels at the Treatment must maintain DA levels at the

set point for survivalset point for survival

Abuse vs. DependenceAbuse vs. Dependence

Drug/Alcohol Drug/Alcohol AbuseAbuse is a is a preventable preventable behaviorbehavior under the control of the PFC under the control of the PFC (judgment)(judgment)– Normal DANormal DA levels in mid-brain levels in mid-brain

Drug/Alcohol Drug/Alcohol DependenceDependence is a is a treatable treatable primary diseaseprimary disease located in the mid-brain, located in the mid-brain, (survival).(survival).– DA deficiencyDA deficiency in mid-brain in mid-brain

Alcohol AbusersAlcohol Abusers

5-year follow-up of ~1,300 men & women5-year follow-up of ~1,300 men & women All met DSM-IV criteria for Abuse onlyAll met DSM-IV criteria for Abuse only 5 years later only 3% met DSM-IV criteria 5 years later only 3% met DSM-IV criteria

for Dependencefor DependenceSchuckit, M.A. et. al., Five year clinical course associated with DSM-Schuckit, M.A. et. al., Five year clinical course associated with DSM-

IV alcohol abuse ……IV alcohol abuse ……Am. J. Pshchiat. 158: 1084-1090Am. J. Pshchiat. 158: 1084-1090

33.7% of all alcoholics who 33.7% of all alcoholics who met DSM-IV criteria for met DSM-IV criteria for Dependence…Dependence…

Did not previously meet Did not previously meet DSM-IV criteria for AbuseDSM-IV criteria for AbuseNESARC 2001-02 study NESARC 2001-02 study

Genetic PredispositionGenetic Predisposition

10% risk with no family history…..10% risk with no family history….. 40% risk with one parent…..40% risk with one parent….. 90+% risk with both parents….90+% risk with both parents….

Chronic ETOH ConsumptionChronic ETOH Consumption

Chronic use of alcohol changes the Chronic use of alcohol changes the genetic makeup of the neurongenetic makeup of the neuron

Changes the structure of the receptor Changes the structure of the receptor proteins, (D2 receptors)proteins, (D2 receptors)

Fewer D2 receptors for DA to bind toFewer D2 receptors for DA to bind to Increased tolerance since more alcohol Increased tolerance since more alcohol

is required to get the same effectis required to get the same effect

The earlier a young person drinks The earlier a young person drinks ETOH, the more likely he/she will ETOH, the more likely he/she will develop a clinically defined alcohol develop a clinically defined alcohol disorder later in lifedisorder later in life

Young people who begin drinking Young people who begin drinking before age 15 are 4x more likely to before age 15 are 4x more likely to develop alcoholism than those who develop alcoholism than those who wait until they are 21 to drinkwait until they are 21 to drink

NIAAA 2000NIAAA 2000

For each year an adolescent For each year an adolescent delays use of alcohol, he/she delays use of alcohol, he/she decreases the odds of decreases the odds of lifelong dependence by 14%, lifelong dependence by 14%, and lifelong abuse by 8%and lifelong abuse by 8%

NIAAA January 2000NIAAA January 2000

When Reading Emotion…Adults Rely More on the Frontal CortexWhile Teens Rely More on the Amygdala

When Reading Emotion…Adults Rely More on the Frontal CortexWhile Teens Rely More on the Amygdala

Deborah Yurgelon-Todd 2000. Deborah Yurgelon-Todd 2000.

Social Structure & DA LevelsSocial Structure & DA Levels Altering social hierarchy in monkeysAltering social hierarchy in monkeys PET scan measurements of DA levelsPET scan measurements of DA levels Higher social status had higher DA levelsHigher social status had higher DA levels Manipulation of the social hierarchy Manipulation of the social hierarchy

causing the higher levels monkeys to be causing the higher levels monkeys to be moved to the lower levels….moved to the lower levels….

DA levels decreased in their NAcDA levels decreased in their NAc

Screening for At-Risk Drinking Screening for At-Risk Drinking How many drinks containing ETOH How many drinks containing ETOH

do you consume per week? Per do you consume per week? Per occasion?occasion?

Men: >14 drinks per weekMen: >14 drinks per week

> 4 drinks per occasion> 4 drinks per occasion Women: > 7 drinks per weekWomen: > 7 drinks per week

> 3 drinks per occasion> 3 drinks per occasion

C.A.G.E.C.A.G.E.C:C: Have you ever tried to Have you ever tried to CCut down on your ut down on your

drinking?drinking?

A:A: Do you become Do you become AAnnoyed when people nnoyed when people talk to you about your drinking?talk to you about your drinking?

G:G: Do you ever feel Do you ever feel GGuilty about your uilty about your drinking?drinking?

E:E: Have you ever had an “ Have you ever had an “EEye Opener” (a ye Opener” (a drink in the morning)drink in the morning)

Positive screen if yes to 2 or morePositive screen if yes to 2 or more

C.R.A.F.F.T.C.R.A.F.F.T.Adolescent ScreeningAdolescent Screening

C:C: Have you ever ridden in a Have you ever ridden in a CCar driven by ar driven by someone (including yourself) who was someone (including yourself) who was “high” or had been using alcohol or “high” or had been using alcohol or drugs?drugs?

R:R: Do you ever use alcohol or drugs to Do you ever use alcohol or drugs to RRelax, feel better about yourself, or to fit elax, feel better about yourself, or to fit in?in?

A:A: Do you ever use alcohol or drugs while Do you ever use alcohol or drugs while you are you are AAlone?lone?

C.R.A.F.F.T.C.R.A.F.F.T.Adolescent ScreeningAdolescent Screening

F:F: Do you ever Do you ever FForget things you did while orget things you did while using drugs or alcohol?using drugs or alcohol?

F:F: Do your Do your FFamily or amily or FFriends ever talk to riends ever talk to you about your drinking or drug use?you about your drinking or drug use?

T:T: Have you gotten into Have you gotten into TTrouble while you rouble while you were using alcohol or drugs?were using alcohol or drugs?

““Yes” to 2 or more is predictive of a Yes” to 2 or more is predictive of a Substance Use DisorderSubstance Use Disorder

How Does the Alcoholic Define How Does the Alcoholic Define Alcoholism?Alcoholism?

The average alcoholic has a family, The average alcoholic has a family, home, job & responsibilityhome, job & responsibility

Only 3% of alcoholics are the stereotype Only 3% of alcoholics are the stereotype “skid row bums” “skid row bums”

The alcoholic will continue to change The alcoholic will continue to change his/her definition…his/her definition…

DSM-IV Substance Dependence>/= 3 of the following in a 12 month period Tolerance Withdrawal Using larger amounts than intended Persistent efforts to cut down or control use Great deal of time spent getting the substance,

taking it, & recovering Important activities given up for using Continued use despite psychological or

physical problems caused by using the substance

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Treatment

Level ILevel I Individual counsellingIndividual counsellingLevel II.1Level II.1 Intensive Outpatient (IOP)Intensive Outpatient (IOP)Level II.5Level II.5 Partial HospitalizationPartial HospitalizationLevel III.1-III.5Level III.1-III.5 Non-hospital ResidentialNon-hospital ResidentialLevel III.7Level III.7 Inpatient Medically MonitoredInpatient Medically MonitoredLevel IVLevel IV General Hospital with ICUGeneral Hospital with ICUAftercare:Aftercare: Facilitated meetings to help Facilitated meetings to help

with reentry to family, work & with reentry to family, work & society (6-12 months)society (6-12 months)

Twelve Step RecoveryTwelve Step RecoveryRobert L. Dupont, M.D. Robert L. Dupont, M.D. 11stst president of NIDA president of NIDA 22ndnd U.S. Drug Czar U.S. Drug Czar The Selfish Brain: learning from addictionThe Selfish Brain: learning from addiction ““The secret weapon in the war on drugs is the The secret weapon in the war on drugs is the

12-Step program”12-Step program” ““12-Step programs are the key to long-term 12-Step programs are the key to long-term

recovery”recovery” ““12-Step recovery is THE ONLY THING THAT 12-Step recovery is THE ONLY THING THAT

WORKS”WORKS”

Georgia Physician’s StudyGeorgia Physician’s Study

At least five 12-Step meetings per weekAt least five 12-Step meetings per week Weekly Caduceus meetingsWeekly Caduceus meetings 77% success at 7 years77% success at 7 years 76% of relapsers remained sober after 2 76% of relapsers remained sober after 2

years with additional treatment years with additional treatment

Extended Abstinence Extended Abstinence is Predictive of Sustained Recoveryis Predictive of Sustained Recovery

It takes a year of abstinence

before less than half relapse

Dennis et al, Eval Rev, 2007

After 5 years – if you are sober, you probably will stay that way.

Incubation of Relapse Propensity Incubation of Relapse Propensity Over TimeOver Time

The longer an individual remains in The longer an individual remains in their old “using” environment their old “using” environment immediately after treatment, the immediately after treatment, the greater the risk of relapsegreater the risk of relapse

This may be measured in daysThis may be measured in days

RelapseRelapse

PreventionPrevention

3 Different Classes of Relapse3 Different Classes of Relapse

Stress mediated: (POMC)Stress mediated: (POMC) ““Cue” mediated (“euphoric recall”)Cue” mediated (“euphoric recall”) Drug mediated: (VTA-to-NAc)Drug mediated: (VTA-to-NAc)

– Cross AddictionCross Addiction– Opiate Rx for legitimate painOpiate Rx for legitimate pain

Stress and RelapseStress and Relapse

Pro-opio-melanocortic (POMC)Pro-opio-melanocortic (POMC) MSH + ACTH + beta-endorphinMSH + ACTH + beta-endorphin Increases Dopamine levels in NAcIncreases Dopamine levels in NAc

CRF antagonists significantly reduced CRF antagonists significantly reduced alcohol consumption in alcohol (P) micealcohol consumption in alcohol (P) mice

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The Memory of Drugs

Nature Video Cocaine Video

Front of Brain

Back of Brain

Amygdalanot lit up

Amygdalaactivated

Cross-AddictionCross-Addiction

Mouthwash containing alcoholMouthwash containing alcohol Cough syrups containing alcoholCough syrups containing alcohol BenadrylBenadryl O’Doule’s (non-alcoholic beer)O’Doule’s (non-alcoholic beer) Prescription SabotagePrescription Sabotage

Prescription SabotagePrescription Sabotage

PropoxyphenePropoxyphene (methadone-related) (methadone-related) Talwin Talwin (opioid agonist-antagonist)(opioid agonist-antagonist) Ultram Ultram (central opioid agonist)(central opioid agonist) Provigil Provigil (narcolepsy, sleep apnea)(narcolepsy, sleep apnea) Lyrica Lyrica

Opiates and PainOpiates and Pain Opiates bind to Mu receptorsOpiates bind to Mu receptors InhibitInhibit the Mu receptors the Mu receptors DecreaseDecrease in adenyl cyclase activity in adenyl cyclase activity DecreaseDecrease in cyclic-AMP in cyclic-AMP IncreaseIncrease in K+ efflux in K+ efflux DecreaseDecrease in Ca++ influx in Ca++ influx HyperpolarizationHyperpolarization of the pain nerve fibers in the of the pain nerve fibers in the

ascending & descending pathways resulting in a ascending & descending pathways resulting in a reduction of painreduction of pain

Prolonged use of a short acting opiate reverses this Prolonged use of a short acting opiate reverses this cascade resulting in increased paincascade resulting in increased pain

Prolonged Opiate UseProlonged Opiate UseDenmark Epidemiological StudyDenmark Epidemiological Study

Chronic opiate use for non-cancer pain Chronic opiate use for non-cancer pain reliefrelief

Denmark has the highest per capita use of Denmark has the highest per capita use of opioids in the worldopioids in the world

Eriksen, Bruera, et.al. Eriksen, Bruera, et.al. Critical issues on opioids in Critical issues on opioids in chronic non-cancer pain.chronic non-cancer pain. An epidemiological study. An epidemiological study. Pain 2006; 125: 172-179Pain 2006; 125: 172-179

Patients reported:Patients reported:

Significantly more painSignificantly more pain Poorer self-rated healthPoorer self-rated health Lower quality of lifeLower quality of life Lower levels of physical activitiyLower levels of physical activitiy Lower levels of employmentLower levels of employment Higher levels of health care utilizationHigher levels of health care utilization

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Tolerance Curve

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Tolerance Curve

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Tolerance Curve

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Tolerance Curve

Increased Mortality After TreatmentIncreased Mortality After Treatment

Mean time of inpatient treatment (54 wks)Mean time of inpatient treatment (54 wks) Highest mortality occurred within the Highest mortality occurred within the

first four weeks after release from first four weeks after release from treatmenttreatment

Fatal overdose was most common causeFatal overdose was most common cause Violence was second leading cause of Violence was second leading cause of

deathdeathRavndal E. Amundsen EJ. Mortality among drug users after Ravndal E. Amundsen EJ. Mortality among drug users after

discharge from inpatient treatment: Drug Alcohol Depend. discharge from inpatient treatment: Drug Alcohol Depend. 2010;108(1-2):65-692010;108(1-2):65-69

Club Drugs:Club Drugs: Ecstasy Ecstasy GHBGHB RohypnolRohypnol KetamineKetamine K2, SpiceK2, Spice Huffing Huffing

EcstasyEcstasy

““XTC”, “X”, “Adam”, “hug”, “beans”, XTC”, “X”, “Adam”, “hug”, “beans”, “love drug”“love drug”

Causes mental stimulation and emotional Causes mental stimulation and emotional warmthwarmth

EcstasyEcstasy

Blocks reuptake of serotonin by nerve Blocks reuptake of serotonin by nerve terminalsterminals

Depletes nerve terminals of serotoninDepletes nerve terminals of serotonin Malignant HyperthermiaMalignant Hyperthermia 2-D-6 enzyme deficiency2-D-6 enzyme deficiency

– Occurs in 10% of the populationOccurs in 10% of the population– Same as increasing the dose 10xSame as increasing the dose 10x

GHBGHB

““G”, “Liquid Ecstasy”, “soap”G”, “Liquid Ecstasy”, “soap” Colorless clear liquid or powderColorless clear liquid or powder CNS depressantCNS depressant Lethal dose very close to therapeutic Lethal dose very close to therapeutic

dosedose May result in sleep, coma, seizures & May result in sleep, coma, seizures &

deathdeath ““date rape drug”date rape drug”

RohypnolRohypnol ““roofies”roofies” Similar effect to Valium, Ativan & XanaxSimilar effect to Valium, Ativan & Xanax Can produce anterograde amnesiaCan produce anterograde amnesia Combined with GHBCombined with GHB

– Cause unconsciousness & temporary Cause unconsciousness & temporary blackout leaving the victim vulnerable to blackout leaving the victim vulnerable to sexual assault with no memory of incidentsexual assault with no memory of incident

Can produce tolerance, physical Can produce tolerance, physical dependence and withdrawal seizuresdependence and withdrawal seizures

Ketamine Ketamine

““Special K”, “Vitamin K”, “Jet”Special K”, “Vitamin K”, “Jet” Dissociative anesthetic used in Dissociative anesthetic used in

veterinary medicineveterinary medicine Distorts perception of sight & soundDistorts perception of sight & sound Potentially fatal respiratory problemsPotentially fatal respiratory problems Users can develop tolerance & cravingsUsers can develop tolerance & cravings

K2, Spice, (JWH-018)K2, Spice, (JWH-018) ““legal marijuana” legal marijuana” Chemically not related to THC but binds to the Chemically not related to THC but binds to the

Cb1 receptors in the brainCb1 receptors in the brain 20x more potent than marijuana20x more potent than marijuana Extremely high BP, CVA, MI, coma, malignant Extremely high BP, CVA, MI, coma, malignant

hyperthermia & deathhyperthermia & death Distinctive odor (incense-like)Distinctive odor (incense-like) Tolerance & Withdrawal SyndromeTolerance & Withdrawal Syndrome Sold legally at truck stops & head shopsSold legally at truck stops & head shops

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Richard L. Hinchman, M.D., FACOG, FASAMRichard L. Hinchman, M.D., FACOG, FASAM

6756 McFarland Rd.6756 McFarland Rd.

Indianapolis, IN 46227-7718Indianapolis, IN 46227-7718

Cell:Cell: (317) 442-0123(317) 442-0123

Fax:Fax: (317) 786-7381(317) 786-7381

rasbc@aol.com